Department of Chemistry, Beijing Key Laboratory for Microanalytical Methods and Instrumentation, Key Laboratory of Bioorganic Phosphorus, Chemistry and Chemical Biology (Ministry of Education), Tsinghua University, Beijing, 100084, China.
Angew Chem Int Ed Engl. 2019 Oct 1;58(40):14167-14172. doi: 10.1002/anie.201908105. Epub 2019 Aug 19.
RNA-cleaving DNAzymes are useful tools for intracellular metal-ion sensing and gene regulation. Incorporating stimuli-responsive modifications into these DNAzymes enables their activities to be spatiotemporally and chemically controlled for more precise applications. Despite the successful development of many caged DNAzymes for light-induced activation, DNAzymes that can be intracellularly activated by chemical inputs of biological importance, such as reactive oxygen species (ROS), are still scarce. ROS like hydrogen peroxide (H O ) and hypochlorite (HClO) are critical mediators of oxidative stress-related cell signaling and dysregulation including activation of immune system as well as progression of diseases and aging. Herein, we report ROS-activable DNAzymes by introducing phenylboronate and phosphorothioate modifications to the Zn -dependent 8-17 DNAzyme. These ROS-activable DNAzymes were orthogonally activated by H O and HClO inside live human and mouse cells.
RNA 切割型 DNA 酶是用于细胞内金属离子传感和基因调控的有用工具。将响应刺激的修饰物整合到这些 DNA 酶中，可以实现其时空和化学控制，从而进行更精确的应用。尽管已经成功开发了许多用于光诱导激活的 DNA 酶，但能够通过生物重要的化学输入（如活性氧 (ROS)）在细胞内激活的 DNA 酶仍然很少。ROS 如过氧化氢 (H O ) 和次氯酸 (HClO) 是与氧化应激相关的细胞信号转导和失调的关键介质，包括免疫系统的激活以及疾病和衰老的进展。在此，我们通过在 Zn 依赖性 8-17 DNA 酶中引入苯硼酸酯和硫代磷酸酯修饰，报告了 ROS 激活型 DNA 酶。这些 ROS 激活型 DNA 酶可在活的人和小鼠细胞内被 H O 和 HClO 正交激活。
